This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Kerr, S. Articles by Hamilton, C. A. Search for Related Content PubMed PubMed Citation Articles by Kerr, S. Articles by Hamilton, C. A. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Medline Plus Health Information High Blood Pressure Related Collections Animal models of human disease Hypertension - basic studies Oxidant stress

(Hypertension. 1999;33:1353-1358.)
© 1999 American Heart Association, Inc.

Scientific Contributions

Superoxide Anion Production Is Increased in a Model of Genetic Hypertension

Role of the Endothelium

Susanne Kerr; M. Julia Brosnan; Martin McIntyre; John L. Reid; Anna F. Dominiczak; Carlene A. Hamilton

From the Department of Medicine and Therapeutics, Western Infirmary, Glasgow, UK.

Correspondence to Dr Carlene A. Hamilton, Department of Medicine and Therapeutics, Western Infirmary, Glasgow G11 6NT, UK.

Abstract—The hypothesis that the decreased nitric oxide (NO) availability observed in spontaneously hypertensive stroke-prone rats (SHRSP) is due to excess superoxide (O₂^-) was examined. O₂^- generation, measured by lucigenin chemiluminescence, was studied in 12- to 16-week male and female Wistar-Kyoto rats (WKY) and SHRSP. In addition, expression of the gene encoding endothelial NO synthase, the enzyme involved in NO generation, was investigated. O₂^- generation was increased in male and female SHRSP (4.11±0.24 and 3.84±0.28 nmol O₂^- · min^-1 · mg^-1 respectively) compared with their WKY counterparts and was significantly higher in male than female WKY (1.22±0.08 in males and 0.8±0.08 nmol O₂^- · min^-1 · mg^-1 respectively) (SHRSP versus WKY P<0.0001, 95% CI -3.39, -2.51; male versus female WKY P=0.0029, 95% CI -0.67, -0.17). Removal of the endothelium by rubbing or addition of NO synthase inhibitors attenuated O₂^- generation in SHRSP but not WKY. In males, removal of the endothelium reduced O₂^- generation from 3.86±0.12 to 1.35±0.08 nmol · min^-1 · mg^-1 (P<0.0001, 95% CI 2.29, 2.81), whereas addition of L-NAME caused a reduction from 4.13±0.17 to 1.32±0.16 nmol · min^-1 · mg^-1 (P<0.0001, 95% CI 2.36, 2.83). Similar reductions were observed in females. L-arginine had no significant effect, but tetrahydrobiopterin significantly decreased O₂^- generation in SHRSP from 4.04±0.11 to 2.36±0.40 nmol · min^-1 · mg^-1 (P=0.0026, 95% CI 0.89, 2.44). Endothelial NO synthase mRNA expression was significantly greater in SHRSP than in WKY and in WKY males than in WKY females. These results show that O₂^- generation is increased in SHRSP and that the tissue and enzymatic sources of this excess O₂^- appear to be the endothelium and eNOS, respectively. The increase in O₂^- generation could explain the decreased availability of basal NO observed in this model of genetic hypertension.

Key Words: superoxide • endothelium • nitric oxide • rats, inbred SHR • nitric oxide synthase

This article has been cited by other articles:

				R. Masson, S. A. Nicklin, M. A. Craig, M. McBride, K. Gilday, P. Gregorevic, J. M. Allen, J. S. Chamberlain, G. Smith, D. Graham, et al. Onset of Experimental Severe Cardiac Fibrosis Is Mediated by Overexpression of Angiotensin-Converting Enzyme 2 Hypertension, April 1, 2009; 53(4): 694 - 700. [Abstract] [Full Text] [PDF]

				K. M. Dunn, M. Renic, A. K. Flasch, D. R. Harder, J. Falck, and R. J. Roman Elevated production of 20-HETE in the cerebral vasculature contributes to severity of ischemic stroke and oxidative stress in spontaneously hypertensive rats Am J Physiol Heart Circ Physiol, December 1, 2008; 295(6): H2455 - H2465. [Abstract] [Full Text] [PDF]

				E. Grossman Does Increased Oxidative Stress Cause Hypertension? Diabetes Care, February 1, 2008; 31(Supplement_2): S185 - S189. [Abstract] [Full Text] [PDF]

				D. Graham, M. W. McBride, M. Gaasenbeek, K. Gilday, E. Beattie, W. H. Miller, J. D. McClure, J. M. Polke, A. Montezano, R. M. Touyz, et al. Candidate Genes That Determine Response to Salt in the Stroke-Prone Spontaneously Hypertensive Rat: Congenic Analysis Hypertension, December 1, 2007; 50(6): 1134 - 1141. [Abstract] [Full Text] [PDF]

				D. Li, L. Wang, C.-W. Lee, T. A. Dawson, and D. J. Paterson Noradrenergic Cell Specific Gene Transfer With Neuronal Nitric Oxide Synthase Reduces Cardiac Sympathetic Neurotransmission in Hypertensive Rats Hypertension, July 1, 2007; 50(1): 69 - 74. [Abstract] [Full Text] [PDF]

				D. A. Heaton, D. Li, S. C. Almond, T. A. Dawson, L. Wang, K. M. Channon, and D. J. Paterson Gene Transfer of Neuronal Nitric Oxide Synthase into Intracardiac Ganglia Reverses Vagal Impairment in Hypertensive Rats Hypertension, February 1, 2007; 49(2): 380 - 388. [Abstract] [Full Text] [PDF]

				M. Feletou and P. M. Vanhoutte Endothelial dysfunction: a multifaceted disorder (The Wiggers Award Lecture) Am J Physiol Heart Circ Physiol, September 1, 2006; 291(3): H985 - H1002. [Abstract] [Full Text] [PDF]

				S. Ye, H. Zhong, and V. M. Campese Oxidative Stress Mediates the Stimulation of Sympathetic Nerve Activity in the Phenol Renal Injury Model of Hypertension Hypertension, August 1, 2006; 48(2): 309 - 315. [Abstract] [Full Text] [PDF]

				U. Forstermann and T. Munzel Endothelial Nitric Oxide Synthase in Vascular Disease: From Marvel to Menace Circulation, April 4, 2006; 113(13): 1708 - 1714. [Abstract] [Full Text] [PDF]

				A. Paliege, A. Parsumathy, D. Mizel, T. Yang, J. Schnermann, and S. Bachmann Effect of apocynin treatment on renal expression of COX-2, NOS1, and renin in Wistar-Kyoto and spontaneously hypertensive rats Am J Physiol Regulatory Integrative Comp Physiol, March 1, 2006; 290(3): R694 - R700. [Abstract] [Full Text] [PDF]

				Z. Yang, L. D. Asico, P. Yu, Z. Wang, J. E. Jones, C. S. Escano, X. Wang, M. T. Quinn, D. R. Sibley, G. G. Romero, et al. D5 dopamine receptor regulation of reactive oxygen species production, NADPH oxidase, and blood pressure Am J Physiol Regulatory Integrative Comp Physiol, January 1, 2006; 290(1): R96 - R104. [Abstract] [Full Text] [PDF]

				L. T. de Richelieu, C. M. Sorensen, N.-H. Holstein-Rathlou, and M. Salomonsson NO-independent mechanism mediates tempol-induced renal vasodilation in SHR Am J Physiol Renal Physiol, December 1, 2005; 289(6): F1227 - F1234. [Abstract] [Full Text] [PDF]

				T. Berg Increased counteracting effect of eNOS and nNOS on an {alpha}1-adrenergic rise in total peripheral vascular resistance in spontaneous hypertensive rats Cardiovasc Res, September 1, 2005; 67(4): 736 - 744. [Abstract] [Full Text] [PDF]

				A. L. Kruger, S. Peterson, S. Turkseven, P. M. Kaminski, F. F. Zhang, S. Quan, M. S. Wolin, and N. G. Abraham D-4F Induces Heme Oxygenase-1 and Extracellular Superoxide Dismutase, Decreases Endothelial Cell Sloughing, and Improves Vascular Reactivity in Rat Model of Diabetes Circulation, June 14, 2005; 111(23): 3126 - 3134. [Abstract] [Full Text] [PDF]

				S. Racasan, B. Braam, H. A. Koomans, and J. A. Joles Programming blood pressure in adult SHR by shifting perinatal balance of NO and reactive oxygen species toward NO: the inverted Barker phenomenon Am J Physiol Renal Physiol, April 1, 2005; 288(4): F626 - F636. [Abstract] [Full Text] [PDF]

				M. W. McBride, M. J. Brosnan, J. Mathers, L. I. McLellan, W. H. Miller, D. Graham, N. Hanlon, C. A. Hamilton, J. M. Polke, W. K. Lee, et al. Reduction of Gstm1 Expression in the Stroke-Prone Spontaneously Hypertension Rat Contributes to Increased Oxidative Stress Hypertension, April 1, 2005; 45(4): 786 - 792. [Abstract] [Full Text] [PDF]

				A. F. Dominiczak, D. Graham, M. W. McBride, N. J.R. Brain, W. K. Lee, F. J. Charchar, M. Tomaszewski, C. Delles, and C. A. Hamilton Cardiovascular Genomics and Oxidative Stress Hypertension, April 1, 2005; 45(4): 636 - 642. [Abstract] [Full Text] [PDF]

				F. A. DeLano, R. Balete, and G. W. Schmid-Schonbein Control of oxidative stress in microcirculation of spontaneously hypertensive rats Am J Physiol Heart Circ Physiol, February 1, 2005; 288(2): H805 - H812. [Abstract] [Full Text] [PDF]

				S. Sela, R. Mazor, M. Amsalam, C. Yagil, Y. Yagil, and B. Kristal Primed Polymorphonuclear Leukocytes, Oxidative Stress, and Inflammation Antecede Hypertension in the Sabra Rat Hypertension, November 1, 2004; 44(5): 764 - 769. [Abstract] [Full Text] [PDF]

				J. M. Williams, J. S. Pollock, and D. M. Pollock Arterial Pressure Response to the Antioxidant Tempol and ETB Receptor Blockade in Rats on a High-Salt Diet Hypertension, November 1, 2004; 44(5): 770 - 775. [Abstract] [Full Text] [PDF]

				V. M. Campese, S. Ye, H. Zhong, V. Yanamadala, Z. Ye, and J. Chiu Reactive oxygen species stimulate central and peripheral sympathetic nervous system activity Am J Physiol Heart Circ Physiol, August 1, 2004; 287(2): H695 - H703. [Abstract] [Full Text] [PDF]

				T. Kishi, Y. Hirooka, Y. Kimura, K. Ito, H. Shimokawa, and A. Takeshita Increased Reactive Oxygen Species in Rostral Ventrolateral Medulla Contribute to Neural Mechanisms of Hypertension in Stroke-Prone Spontaneously Hypertensive Rats Circulation, May 18, 2004; 109(19): 2357 - 2362. [Abstract] [Full Text] [PDF]

				F. K Shieh, E. Kotlyar, and F. Sam Aldosterone and cardiovascular remodelling: focus on myocardial failure Journal of Renin-Angiotensin-Aldosterone System, March 1, 2004; 5(1): 3 - 13. [Abstract] [PDF]

				A. Nishiyama, M. Yoshizumi, H. Hitomi, S. Kagami, S. Kondo, A. Miyatake, M. Fukunaga, T. Tamaki, H. Kiyomoto, M. Kohno, et al. The SOD Mimetic Tempol Ameliorates Glomerular Injury and Reduces Mitogen-Activated Protein Kinase Activity in Dahl Salt-Sensitive Rats J. Am. Soc. Nephrol., February 1, 2004; 15(2): 306 - 315. [Abstract] [Full Text] [PDF]

				J. Zhu, T. Mori, T. Huang, and J. H. Lombard Effect of high-salt diet on NO release and superoxide production in rat aorta Am J Physiol Heart Circ Physiol, February 1, 2004; 286(2): H575 - H583. [Abstract] [Full Text] [PDF]

				S. CUZZOCREA, E. MAZZON, L. DUGO, R. DI PAOLA, A. P. CAPUTI, and D. SALVEMINI Superoxide: a key player in hypertension FASEB J, January 1, 2004; 18(1): 94 - 101. [Abstract] [Full Text] [PDF]

				H. Negishi, J.-W. Xu, K. Ikeda, M. Njelekela, Y. Nara, and Y. Yamori Black and Green Tea Polyphenols Attenuate Blood Pressure Increases in Stroke-Prone Spontaneously Hypertensive Rats J. Nutr., January 1, 2004; 134(1): 38 - 42. [Abstract] [Full Text] [PDF]

				A. P. V Dantas, M. d. C. P Franco, M. M Silva-Antonialli, R. C.A Tostes, Z. B Fortes, D. Nigro, and M. H. C Carvalho Gender differences in superoxide generation in microvessels of hypertensive rats: role of NAD(P)H-oxidase Cardiovasc Res, January 1, 2004; 61(1): 22 - 29. [Abstract] [Full Text] [PDF]

				P. Minuz, P. Patrignani, S. Gaino, F. Seta, M. L. Capone, S. Tacconelli, M. Degan, G. Faccini, A. Fornasiero, G. Talamini, et al. Determinants of Platelet Activation in Human Essential Hypertension Hypertension, January 1, 2004; 43(1): 64 - 70. [Abstract] [Full Text] [PDF]

				J. P. Dina, T. Feres, A. C.M. Paiva, and T. B. Paiva Role of Membrane Potential and Expression of Endothelial Factors in Restenosis After Angioplasty in SHR Hypertension, January 1, 2004; 43(1): 131 - 135. [Abstract] [Full Text] [PDF]

				Y.-F. Chen, A. W. Cowley Jr., and A.-P. Zou Increased H2O2 counteracts the vasodilator and natriuretic effects of superoxide dismutation by tempol in renal medulla Am J Physiol Regulatory Integrative Comp Physiol, October 1, 2003; 285(4): R827 - R833. [Abstract] [Full Text] [PDF]

				A. R. Chade, M. Rodriguez-Porcel, J. Herrmann, J. D. Krier, X. Zhu, A. Lerman, and L. O. Lerman Beneficial Effects of Antioxidant Vitamins on the Stenotic Kidney Hypertension, October 1, 2003; 42(4): 605 - 612. [Abstract] [Full Text] [PDF]

				P. Biglioli, A. Cannata, F. Alamanni, M. Naliato, M. Porqueddu, M. Zanobini, E. Tremoli, and A. Parolari Biological effects of off-pump vs. on-pump coronary artery surgery: focus on inflammation, hemostasis and oxidative stress Eur. J. Cardiothorac. Surg., August 1, 2003; 24(2): 260 - 269. [Abstract] [Full Text] [PDF]

				S. Ulker, D. McMaster, P. P. McKeown, and U. Bayraktutan Impaired activities of antioxidant enzymes elicit endothelial dysfunction in spontaneous hypertensive rats despite enhanced vascular nitric oxide generation Cardiovasc Res, August 1, 2003; 59(2): 488 - 500. [Abstract] [Full Text] [PDF]

				S. Meng, G. W. Cason, A. W. Gannon, L. C. Racusen, and R. D. Manning Jr Oxidative Stress in Dahl Salt-Sensitive Hypertension Hypertension, June 1, 2003; 41(6): 1346 - 1352. [Abstract] [Full Text] [PDF]

				J. Ibrahim, J. K. Miyashiro, and B. C. Berk Shear Stress Is Differentially Regulated Among Inbred Rat Strains Circ. Res., May 16, 2003; 92(9): 1001 - 1009. [Abstract] [Full Text] [PDF]

				J. Ou, Z. Ou, D. G. McCarver, R. N. Hines, K. T. Oldham, A. W. Ackerman, and K. A. Pritchard Jr. Trichloroethylene Decreases Heat Shock Protein 90 Interactions with Endothelial Nitric Oxide Synthase: Implications for Endothelial Cell Proliferation Toxicol. Sci., May 1, 2003; 73(1): 90 - 97. [Abstract] [Full Text] [PDF]

				J. F. Reckelhoff and J. C. Romero Role of oxidative stress in angiotensin-induced hypertension Am J Physiol Regulatory Integrative Comp Physiol, April 1, 2003; 284(4): R893 - R912. [Abstract] [Full Text] [PDF]

				S. Ulker, P. P. McKeown, and U. Bayraktutan Vitamins Reverse Endothelial Dysfunction Through Regulation of eNOS and NAD(P)H Oxidase Activities Hypertension, March 1, 2003; 41(3): 534 - 539. [Abstract] [Full Text] [PDF]

				K. M. Hoagland, K. G. Maier, and R. J. Roman Contributions of 20-HETE to the Antihypertensive Effects of Tempol in Dahl Salt-Sensitive Rats Hypertension, March 1, 2003; 41(3): 697 - 702. [Abstract] [Full Text] [PDF]

				M. W. McBride, F. J. Carr, D. Graham, N. H. Anderson, J. S. Clark, W. K. Lee, F. J. Charchar, M. J. Brosnan, and A. F. Dominiczak Microarray Analysis of Rat Chromosome 2 Congenic Strains Hypertension, March 1, 2003; 41(3): 847 - 853. [Abstract] [Full Text] [PDF]

				A. Piech, C. Dessy, X. Havaux, O. Feron, and J.-L. Balligand Differential regulation of nitric oxide synthases and their allosteric regulators in heart and vessels of hypertensive rats Cardiovasc Res, February 1, 2003; 57(2): 456 - 467. [Abstract] [Full Text] [PDF]

				T. Shokoji, A. Nishiyama, Y. Fujisawa, H. Hitomi, H. Kiyomoto, N. Takahashi, S. Kimura, M. Kohno, and Y. Abe Renal Sympathetic Nerve Responses to Tempol in Spontaneously Hypertensive Rats Hypertension, February 1, 2003; 41(2): 266 - 273. [Abstract] [Full Text] [PDF]

				D. Yang, N. Levens, J. N. Zhang, P. M. Vanhoutte, and M. Feletou Specific Potentiation of Endothelium-Dependent Contractions in SHR by Tetrahydrobiopterin Hypertension, January 1, 2003; 41(1): 136 - 142. [Abstract] [Full Text] [PDF]

				Y. Sun, J. Zhang, L. Lu, S. S. Chen, M. T. Quinn, and K. T. Weber Aldosterone-Induced Inflammation in the Rat Heart : Role of Oxidative Stress Am. J. Pathol., November 1, 2002; 161(5): 1773 - 1781. [Abstract] [Full Text] [PDF]

				L. V. Rossoni, M. Salaices, M. Miguel, A. M. Briones, L. A. Barker, D. V. Vassallo, and M. J. Alonso Ouabain-induced hypertension is accompanied by increases in endothelial vasodilator factors Am J Physiol Heart Circ Physiol, November 1, 2002; 283(5): H2110 - H2118. [Abstract] [Full Text] [PDF]

				C. A. Hamilton, M. J. Brosnan, S. Al-Benna, G. Berg, and A. F. Dominiczak NAD(P)H Oxidase Inhibition Improves Endothelial Function in Rat and Human Blood Vessels Hypertension, November 1, 2002; 40(5): 755 - 762. [Abstract] [Full Text] [PDF]

				A. Sato, H. Miura, Y. Liu, L. B. Somberg, M. F. Otterson, M. J. Demeure, W. J. Schulte, L. M. Eberhardt, F. R. Loberiza, I. Sakuma, et al. Effect of gender on endothelium-dependent dilation to bradykinin in human adipose microvessels Am J Physiol Heart Circ Physiol, September 1, 2002; 283(3): H845 - H852. [Abstract] [Full Text] [PDF]

				Q. Hu, Z.-X. Yu, V. J. Ferrans, K. Takeda, K. Irani, and R. C. Ziegelstein Critical Role of NADPH Oxidase-derived Reactive Oxygen Species in Generating Ca2+ Oscillations in Human Aortic Endothelial Cells Stimulated by Histamine J. Biol. Chem., August 30, 2002; 277(36): 32546 - 32551. [Abstract] [Full Text] [PDF]

				D. M. Lenda and M. A. Boegehold Effect of a high-salt diet on oxidant enzyme activity in skeletal muscle microcirculation Am J Physiol Heart Circ Physiol, February 1, 2002; 282(2): H395 - H402. [Abstract] [Full Text] [PDF]

				A. E. Midaoui and J. de Champlain Prevention of Hypertension, Insulin Resistance, and Oxidative Stress by {alpha}-Lipoic Acid Hypertension, February 1, 2002; 39(2): 303 - 307. [Abstract] [Full Text] [PDF]

				Y. Ren, O. A. Carretero, and J. L. Garvin Mechanism by Which Superoxide Potentiates Tubuloglomerular Feedback Hypertension, February 1, 2002; 39(2): 624 - 628. [Abstract] [Full Text] [PDF]

				A. Makino, M. M. Skelton, A.-P. Zou, R. J. Roman, and A. W. Cowley Jr Increased Renal Medullary Oxidative Stress Produces Hypertension Hypertension, February 1, 2002; 39(2): 667 - 672. [Abstract] [Full Text] [PDF]

				G. Wiemer, G. Itter, T. Malinski, and W. Linz Decreased Nitric Oxide Availability in Normotensive and Hypertensive Rats With Failing Hearts After Myocardial Infarction Hypertension, December 1, 2001; 38(6): 1367 - 1371. [Abstract] [Full Text] [PDF]

				G. Zalba, G. S. Jose, M. U. Moreno, M. A. Fortuno, A. Fortuno, F. J. Beaumont, and J. Diez Oxidative Stress in Arterial Hypertension: Role of NAD(P)H Oxidase Hypertension, December 1, 2001; 38(6): 1395 - 1399. [Abstract] [Full Text] [PDF]

				R. M Bell and D. M Yellon The contribution of endothelial nitric oxide synthase to early ischaemic preconditioning: the lowering of the preconditioning threshold. An investigation in eNOS knockout mice Cardiovasc Res, November 1, 2001; 52(2): 274 - 280. [Abstract] [Full Text] [PDF]

				X.-L. Ma, F. Gao, A. H. Nelson, B. L. Lopez, T. A. Christopher, T.-L. Yue, and F. C. Barone Oxidative Inactivation of Nitric Oxide and Endothelial Dysfunction in Stroke-Prone Spontaneous Hypertensive Rats J. Pharmacol. Exp. Ther., September 1, 2001; 298(3): 879 - 885. [Abstract] [Full Text]

				X. Chen, R. M. Touyz, J. B. Park, and E. L. Schiffrin Antioxidant Effects of Vitamins C and E Are Associated With Altered Activation of Vascular NADPH Oxidase and Superoxide Dismutase in Stroke-Prone SHR Hypertension, September 1, 2001; 38(3): 606 - 611. [Abstract] [Full Text] [PDF]

				S. M Bryant, C. E Sears, L. Rigg, D. A Terrar, and B. Casadei Nitric oxide does not modulate the hyperpolarization-activated current, If, in ventricular myocytes from spontaneously hypertensive rats Cardiovasc Res, July 1, 2001; 51(1): 51 - 58. [Abstract] [Full Text] [PDF]

				P. Krenek, S. Salomone, J. Kyselovic, M. Wibo, N. Morel, and T. Godfraind Lacidipine Prevents Endothelial Dysfunction in Salt-Loaded Stroke-Prone Hypertensive Rats Hypertension, April 1, 2001; 37(4): 1124 - 1128. [Abstract] [Full Text] [PDF]

				C. A. Hamilton, M. J. Brosnan, M. McIntyre, D. Graham, and A. F. Dominiczak Superoxide Excess in Hypertension and Aging : A Common Cause of Endothelial Dysfunction Hypertension, February 1, 2001; 37(2): 529 - 534. [Abstract] [Full Text] [PDF]

				A. Ichihara, M. Hayashi, N. Hirota, and T. Saruta Superoxide Inhibits Neuronal Nitric Oxide Synthase Influences on Afferent Arterioles in Spontaneously Hypertensive Rats Hypertension, February 1, 2001; 37(2): 630 - 634. [Abstract] [Full Text] [PDF]

				R. A. Beswick, H. Zhang, D. Marable, J. D. Catravas, W. D. Hill, and R. C. Webb Long-Term Antioxidant Administration Attenuates Mineralocorticoid Hypertension and Renal Inflammatory Response Hypertension, February 1, 2001; 37(2): 781 - 786. [Abstract] [Full Text] [PDF]

				J.-M. R. Frenoux, E. D. Prost, J. L. Belleville, and J. L. Prost A Polyunsaturated Fatty Acid Diet Lowers Blood Pressure and Improves Antioxidant Status in Spontaneously Hypertensive Rats J. Nutr., January 1, 2001; 131(1): 39 - 45. [Abstract] [Full Text]

				T. Matsunaga, D. C. Warltier, D. W. Weihrauch, M. Moniz, J. Tessmer, and W. M. Chilian Ischemia-Induced Coronary Collateral Growth Is Dependent on Vascular Endothelial Growth Factor and Nitric Oxide Circulation, December 19, 2000; 102(25): 3098 - 3103. [Abstract] [Full Text] [PDF]

				H. Cai and D. G. Harrison Endothelial Dysfunction in Cardiovascular Diseases: The Role of Oxidant Stress Circ. Res., November 10, 2000; 87(10): 840 - 844. [Abstract] [Full Text] [PDF]

				M.Y. Alexander, M.J. Brosnan, C. A. Hamilton, J. P. Fennell, E. C. Beattie, E. Jardine, D. D. Heistad, and A. F. Dominiczak Gene transfer of endothelial nitric oxide synthase but not Cu/Zn superoxide dismutase restores nitric oxide availability in the SHRSP Cardiovasc Res, August 18, 2000; 47(3): 609 - 617. [Abstract] [Full Text] [PDF]

				K. M. Channon, H. Qian, and S. E. George Nitric Oxide Synthase in Atherosclerosis and Vascular Injury : Insights From Experimental Gene Therapy Arterioscler. Thromb. Vasc. Biol., August 1, 2000; 20(8): 1873 - 1881. [Abstract] [Full Text] [PDF]

				G. Lembo, C. Vecchione, R. Izzo, L. Fratta, D. Fontana, G. Marino, G. Pilato, and B. Trimarco Noradrenergic Vascular Hyper-Responsiveness in Human Hypertension Is Dependent on Oxygen Free Radical Impairment of Nitric Oxide Activity Circulation, August 1, 2000; 102(5): 552 - 557. [Abstract] [Full Text] [PDF]

				K. Asai, R. K. Kudej, Y.-T. Shen, G.-P. Yang, G. Takagi, A. B. Kudej, Y.-J. Geng, N. Sato, J. B. Nazareno, D. E. Vatner, et al. Peripheral Vascular Endothelial Dysfunction and Apoptosis in Old Monkeys Arterioscler. Thromb. Vasc. Biol., June 1, 2000; 20(6): 1493 - 1499. [Abstract] [Full Text] [PDF]

				C. Berry, C. A. Hamilton, M. J. Brosnan, F. G. Magill, G. A. Berg, J. J. V. McMurray, and A. F. Dominiczak Investigation Into the Sources of Superoxide in Human Blood Vessels : Angiotensin II Increases Superoxide Production in Human Internal Mammary Arteries Circulation, May 9, 2000; 101(18): 2206 - 2212. [Abstract] [Full Text] [PDF]

				G. Zalba, F. J. Beaumont, G. S. Jose, A. Fortuno, M. A. Fortuno, J. C. Etayo, and J. Diez Vascular NADH/NADPH Oxidase Is Involved in Enhanced Superoxide Production in Spontaneously Hypertensive Rats Hypertension, May 1, 2000; 35(5): 1055 - 1061. [Abstract] [Full Text] [PDF]

				E. Hsich, B. H. Segal, P. J. Pagano, F. E. Rey, B. Paigen, J. Deleonardis, R. F. Hoyt, S. M. Holland, and T. Finkel Vascular Effects Following Homozygous Disruption of p47phox : An Essential Component of NADPH Oxidase Circulation, March 21, 2000; 101(11): 1234 - 1236. [Abstract] [Full Text] [PDF]

				M. McIntyre, D. F. Bohr, and A. F. Dominiczak Endothelial Function in Hypertension : The Role of Superoxide Anion Hypertension, October 1, 1999; 34(4): 539 - 545. [Abstract] [Full Text] [PDF]

				M.Y. Alexander, M.J. Brosnan, C. A Hamilton, P. Downie, A. M Devlin, F. Dowell, W. Martin, H. M Prentice, T. O'Brien, and A. F Dominiczak Gene transfer of endothelial nitric oxide synthase improves nitric oxide-dependent endothelial function in a hypertensive rat model Cardiovasc Res, August 15, 1999; 43(3): 798 - 807. [Abstract] [Full Text] [PDF]

				J. Hoffmann, J. Haendeler, A. Aicher, L. Rossig, M. Vasa, A. M. Zeiher, and S. Dimmeler Aging Enhances the Sensitivity of Endothelial Cells Toward Apoptotic Stimuli: Important Role of Nitric Oxide Circ. Res., October 12, 2001; 89(8): 709 - 715. [Abstract] [Full Text] [PDF]

				S. Wassmann, U. Laufs, D. Stamenkovic, W. Linz, J.-P. Stasch, K. Ahlbory, R. Rosen, M. Bohm, and G. Nickenig Raloxifene Improves Endothelial Dysfunction in Hypertension by Reduced Oxidative Stress and Enhanced Nitric Oxide Production Circulation, April 30, 2002; 105(17): 2083 - 2091. [Abstract] [Full Text] [PDF]